Topic:Pharmacodynamics
Pharmacodynamics in horses refers to the study of how drugs affect the equine body, encompassing the mechanisms of action, the relationship between drug concentration and effect, and the duration of these effects. This field examines how drugs interact with biological systems in horses to produce therapeutic or adverse effects. Key aspects include receptor binding, post-receptor effects, and chemical interactions. Understanding pharmacodynamics is essential for determining appropriate dosages, predicting drug interactions, and assessing therapeutic outcomes in equine medicine. This page compiles peer-reviewed research studies and scholarly articles that explore the pharmacodynamic properties of various drugs in horses, focusing on their effects, efficacy, and safety profiles.
Influence of furosemide on the detection of flunixin meglumine in horse urine samples. The possibility of false negative results from TLC when a diuretic is administered concomitantly with flunixin was studied. Samples were subjected to solvent extraction from acidic aqueous solutions; duplicate samples were also subjected to alkaline hydrolysis at pH 12.5. The internal standard was flufenamic acid. The quantification of flunixin was performed by HPLC and the results confirmed by GC/MS. The data show that furosemide influences the urinary concentration of flunixin.
Plasma disposition and tolerance of aditoprim in horses after single intravenous injection. Aditoprim, a broad spectrum antimicrobial agent acting as a reversible dihydrofolate reductase inhibitor, was intravenously injected into four 12 to 24-year old horses at a dosage of 5 mg/kg b. w. Blood samples were collected over a 48-hour period after drug injection, and the separated plasma samples were assayed for aditoprim by high performance liquid chromatography. The body temperature, heart rate, respiration rate, and behaviour were recorded during the experiment. The bilirubin and urea concentrations were also determined in several plasma samples, and liver function tests were carried ...
Effect of clenbuterol on arterial oxygen tension in the anaesthetised horse. In horses in dorsal recumbency, spontaneously breathing oxygen, with halothane at a constant end-tidal concentration, the arterial oxygen tension (PO2) increased from 9.9 +/- 0.3 SEM kPa to 21.7 +/- 4.0 kPa with 0.8 micrograms kg-1 clenbuterol and to 29.1 +/- 3.8 kPa with 2.4 micrograms kg-1 clenbuterol. In horses initially in dorsal recumbency then turned to sternal recumbency the PaO2 rose to 54.0 +/- 3.0 kPa, but this rise was unaffected by clenbuterol administration. The response in dorsal recumbency was consistent with clenbuterol counteracting the factor postulated to direct the pulmonar...
Propafenone kinetics in the horse. Comparative analysis of compartmental and noncompartmental models. The propafenone kinetics after intravenous (i.v.) administration have been studied in the horse by a comparative analysis of compartmental and noncompartmental models. The pharmacokinetic parameters showed a large distribution (Vdss = 1021 +/- 211 L) and a high clearance (CI = 7019 +/- 1746 mL/min) of the drug. The plasma concentrations were very low, under 1 microgram/mL, in most cases; after 30 min these concentrations can be considered as nonefficient for the treatment of arrhythmia. There were no significant differences between pharmacokinetic parameters found with the use of compartmental...
Use of gonadotropin-releasing hormone for hastening ovulation in transitional mares. Natural GnRH and its analog have potential for hastening ovulation in mares. A study was conducted to evaluate the efficacy of a GnRH agonist given either as an injectable or s.c. implant for induction of ovulation in mares. Forty-five seasonally anestrous mares (March) were assigned to one of three groups (n = 15/group): 1) untreated controls; 2) i.m. injection of the GnRH agonist buserelin at 12-h intervals (40 micrograms/injection for 28 d or until ovulation) and 3) GnRH agonist administered as a s.c. implant (approximately 100 micrograms/24 h for 28 d). Six mares per group were bled on d 0...
The influence of furosemide on plasma elimination and urinary excretion of drugs in standardbred horses. A study of the effects of intravenous administration of either 150 mg or 250 mg of furosemide to standardbred mares pre-treated with other drugs was undertaken to determine whether a unique pattern of drug elimination into urine and from plasma for each compound occurred. Furosemide significantly reduced the plasma concentrations of codeine compared to control 2-6 h after furosemide administration. In contrast, the plasma concentrations of theophylline, phenylbutazone, pentazocine, guaifenesin and flunixin were not markedly altered by furosemide. In the case of acepromazine, clenbuterol and fe...
Pharmacodynamic evaluation of the peripheral pain inhibition by carprofen and flunixin in the horse. Carprofen, flunixin meglumine and placebo in the form of a physiological solution of sodium chloride were tested in an open randomised cross-over trial for analgesic efficacy in horses with two external skin-stimulation systems. Both systems, the withers model and the "heating element" model, were compared in order to find an optimal way to measure pain perception after stimulating the skin with high temperature. No analgesic effect of flunixin or carprofen could be demonstrated when using the withers model. In the "heating element" model, a 1.1 mg/kg i.v. dose of flunixin meglumine failed to ...
Effects of indomethacin on neural and myogenic components in equine airway smooth muscle. Equine airway smooth muscle is innervated by vagal efferents and, in addition, displays spontaneous mechanical activity. The preparation thus appears to contain at least two discrete excitable components, the cholinergic neural elements and the smooth muscle membrane. Indomethacin (INDO), a cyclooxygenase (CO) inhibitor, exerts a considerable potentiation of function in this preparation. The latter may be effected indirectly, through loss of the inhibitory effect of endogenous prostaglandin E2 (PGE2) on neural acetylcholine release and through direct effects on smooth muscle of the generally a...
[Anesthesia by injection of xylazine, ketamine and the benzodiazepine derivative climazolam and the use of the benzodiazepine antagonist Ro 15-3505]. 25 horses which entered the clinic for minor surgery, received ketamine (2.2 mg/kg i.v.) for induction of anesthesia after previous sedation with xylazine (1.1 mg/kg i.v.). As soon as the horses were in the lateral recumbency, the benzodiazepine derivate climazolam was administered at a dose of 0.1 mg/kg i.v. (10 horses) or 0.2 mg/kg i.v. (15 horses). The anesthesia was maintained with repeated injections of ketamine (1.1 mg/kg i.v. every 9-12 minutes). At the end of the surgery, 20 minutes after the last ketamine injection, Ro 15-3505, a benzodiazepine antagonist, was injected at a dose of 0....
Haemodynamic changes during sedation in ponies. The cardiovascular changes induced by several sedatives were investigated in five ponies with a subcutaneously transposed carotid artery by means of cardiac output determinations (thermodilution technique), systemic and pulmonary artery pressure measurements (direct intravascular method) and arterial blood analysis (blood gases and packed cell volume). The cardiovascular depression (decrease in systemic blood pressure and cardiac output) was long lasting (greater than 90 min) after administration of propionylpromazine (0.08 mg/kg intravenous (i.v.)) together with promethazine (0.08 mg/kg i.v.)...
An evaluation of the multiple-breath nitrogen washout as a pulmonary function test in horses. Multiple-breath nitrogen washouts (MBNW) were performed with 29 light horses. Seven normal horses were used to examine the reproducibility, and 22, ranging from normal to severely diseased, were used to examine the changes in chronic obstructive pulmonary disease (COPD) and the effect of a bronchodilator, salbutamol, on the distribution of ventilation. The MBNW were analyzed using the functional residual capacity (FRC), end-tidal N2 concentration of the final breath of the MBNW (FETN2,fb), end-tidal N2 concentration when the cumulative expired volume was equal to body weight (FETN2,bw), lung c...
Effect of calcium-channel blockers and salbutamol on the isolated mare uterus–interaction with the calcium agonist Bay K 8644. The effects of nifedipine, verapamil and diltiazem were investigated in the isolated mare uterus in comparison with salbutamol. All the calcium-channel blockers and salbutamol inhibited the spontaneous, KC1- and electrically induced contractions; nifedipine and salbutamol were the most potent compounds. The calcium agonist Bay K 8644 (10(-8)-10(-6) mol/l) competitively antagonized the inhibitory effect of nifedipine (pA2 value = 8.54 +/- 0.06), whereas it was only slightly or totally ineffective against verapamil, diltiazem and salbutamol. These results indicate that calcium-channel blockers a...
Antagonism in isolated equine digital vessels of contraction induced by epinephrine in the presence of hydrocortisone and an aqueous extract of black walnut (Juglans nigra). Prazosin, isoxsuprine, and nifedipine were screened for ability to reverse contraction of isolated equine digital vascular strips produced by epinephrine (Epi) in the presence of hydrocortisone (Hc) and an aqueous extract of black walnut (Juglans nigra) (BW). Two arteries and two veins from each of three horses for each drug (n = 9) were maintained in isolated tissue baths in Krebs' bicarbonate buffer with 95% oxygen at 37 degrees C. Six-point Epi concentration-response (C-R) curves were obtained for each vessel in the presence of Hc, BW, and the appropriate vehicle. This was repeated for each...
Pharmacokinetic disposition of an immediate-release aminophylline and a sustained-release theophylline formulation in the horse. The pharmacokinetic disposition of theophylline was determined by high-performance liquid chromatographic analysis of plasma samples from six healthy, adult horses following the administration of intravenous aminophylline (dosed at 9.94 mg/kg as theophylline), immediate-release aminophylline tablets (dosed at 9.94 mg/kg as theophylline), and sustained-release theophylline tablets (dosed at 20 mg/kg). The elimination rate constant (lambda z), apparent volume of distribution (Vz), and clearance (Cl) determined by compartmental analysis of the intravenous data were 0.07 +/- 0.01 h-1, 0.80 +/- 0.0...
Effects of fenoldopam on cecal blood flow and mechanical activity in horses. Lateral cecal arterial blood flow, carotid arterial pressure, heart rate, and mechanical activity in the duodenum, right ventral colon, cecal body, and cecal apex were measured in 6 conscious healthy horses for 60 minutes during and for 120 minutes after IV infusion of 0.9% NaCl solution (control) or fenoldopam. There were no significant changes in these measurements during or after infusion of 0.9% NaCl (saline) solution. Fenoldopam, a selective dopamine-1 receptor agonist, was administered in saline solution at dosages of 0.01, 0.05, and 0.1 micrograms/kg/min. Intravenous infusion of fenoldo...
Effect of probenecid administration on cephapirin pharmacokinetics and concentrations in mares. Cephapirin (20 mg/kg of body weight, IV) was administered before and after 3 doses of probenecid (25, 50, or 75 mg/kg, intragastrically, at 12-hour intervals) to 2 mares. Clearance and apparent volume of distribution, based on area under the curve, were negatively correlated with probenecid dose. Clearance of cephapirin was decreased by approximately 50% by administration of 50 mg of probenecid/kg. Serum, synovial fluid, peritoneal fluid, CSF, urinary, and endometrial concentrations of cephapirin were determined after 5 doses of cephapirin (20 mg/kg, IM, at 12-hour intervals) without and with ...
Isoproterenol- and salbutamol-induced relaxation of acetylcholine- and histamine-induced contraction of equine trachealis muscle in vitro. Strips of trachealis muscle were dissected from the midcervical portion of the trachea of horses that were free of respiratory tract disease, and the overlying epithelium and mucosa were removed. Muscle strips were suspended in tissue baths that were filled with Krebs-bicarbonate solution, aerated with 5% CO2 in oxygen and maintained at 37 C. Isometric tension was continuously recorded. The increase in active isometric tension was concentration dependent when acetylcholine (10(-9) to 10(-4) M) or histamine (10(-9) to 10(-4) M) was added to the tissue baths in 0.5-logarithmic increments. When t...
Effects of pharmacological agents on gastrointestinal motility. The control mechanisms of gastrointestinal motility are complex. Extrinsic neurohormonal effects modulate an intrinsic system, often called the "gut brain," composed of nervous and neuropeptide components. To exert pharmacologic influence on GI motility, use is made of agents that mimic the external control system. Agents that stimulate opioid receptors, block adrenoceptors, block or facilitate acetylcholine action, or antagonize the action of prostaglandins are used to effect changes in GI motility. The major indications for pharmacologic intervention are to increase motility in constipation,...
Functional and ligand binding studies suggest heterogeneity of platelet prostacyclin receptors. 1. This study describes attempts to compare prostacyclin (IP-) receptors in human, pig, horse, rabbit and rat platelets and in circular muscle of human, rabbit and dog mesenteric and pig gastroepiploic arteries. Three stable prostacyclin analogues, iloprost, cicaprost and 6a-carba-prostacyclin (6a-carba-PGI2) and a prostaglandin endoperoxide analogue EP 157 (previously shown to mimic prostacyclin on human platelets) were used. 2. Our main conclusion is that prostacyclin receptors on human, pig and horse platelets are similar in nature, but distinct from those on rabbit and rat platelets. Funct...
Field trial evaluation of detomidine as a sedative and analgesic in horses with colic. In this uncontrolled clinical study 12 investigators cooperated to evaluate the analgesic and sedative effect of detomidine (DORMOSEDAN; Farmos Group Ltd; Finland) in 234 horses with abdominal pain caused by colic. The study was designed to use each animal as its own control and to evaluate its response to the drug over a 60 min period. Detomidine was given intravenously (i.v.) once in 169 cases (167 horses, 1 mule, 1 donkey) at a dose of 20 micrograms/kg bodyweight (bwt), and to 65 horses at 40 micrograms/kg bwt. The higher dose was used predominantly in horses with severe pain which were mor...
Antagonism of endotoxin-induced disruption of equine bowel motility by flunixin and phenylbutazone. Post operative ileus is a serious complication of abdominal surgery in horses and there is evidence that endotoxin plays a significant role in its pathogenesis. Pre-treatment with intravenous (i.v.) flunixin (1.1 mg/kg bodyweight [bwt]) or phenylbutazone (4.4 mg/kg bwt) significantly antagonised the acute disruption of gastric, small intestinal and large intestinal motility induced by 0.1 microgram/kg bwt i.v. endotoxin in ponies implanted with gastrointestinal strain gauges. Phenylbutazone was more effective than flunixin and this was significant (P < 0.01) for the stomach and left dorsal col...
Body fluid and endometrial concentrations of ketoconazole in mares after intravenous injection or repeated gavage. After single oral administration of ketoconazole (30 mg/kg bodyweight [bwt]) in 50 ml of corn syrup to a healthy mare, the drug was not detected in serum. Ketoconazole in 0.2 N HC1 was administered intragastrically to six healthy adult horses in five consecutive doses of 30 mg/kg bwt at 12 h intervals. Ketoconazole concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine and endometrium. Mean peak serum ketoconazole concentration was 3.76 micrograms/ml at 1.5 to 2 h after intragastric administration. Mean peak synovial concentration was 0.87 mic...
Urinary excretion of pentoxifylline and its metabolites by standardbred mares. The urinary excretion of a sustained-release formulation of pentoxifylline was studied in the horse after the oral administration of 4.0 grams of Trental tablets. Urine samples were collected for 24 hours after dosing and analyzed for pentoxifylline and its metabolites using high-performance liquid chromatography coupled with an ultraviolet detector. Six metabolites of pentoxifylline were identified in horse urine in addition to less than 0.2% of unchanged drug. Concomitant use of gas chromatography/mass spectrometry allowed for the elucidation of the chemical structures of the metabolites. Me...
Clinical and pathological effects of flunixin meglumine administration to neonatal foals. The effects of daily intravenous administration of flunixin meglumine at dosages of 0.55, 1.1, 2.2 and 6.6 mg/kg for five days were examined in neonatal foals. Six two day old foals were used to evaluate the effect of each dosage. Foals were examined every day and blood samples collected on days 1, 3 and 6. All foals were euthanized after six days, necropsied and examined for lesions. The major clinical abnormality was diarrhea, but the incidence was not related to the dosage of flunixin meglumine administered. The foals receiving 6.6 mg/kg of flunixin meglumine had significantly more gastroin...
Immunoassay detection of drugs in racing horses. IX. Detection of detomidine in equine blood and urine by radioimmunoassay. Detomidine is a potent non-narcotic sedative agent which is currently in the process of being approved for veterinary clinical use in the United States. Since no effective screening method in horses is available for detomidine, we have developed an 125I radioimmunoassay for detomidine in equine blood and urine as part of a panel of tests for illegal drugs in performance horses. Our 125I radioimmunoassay has an I-50 for detomidine of approximately 2 ng/ml. Our assay shows limited cross-reactivity with the pharmacodynamically similar xylazine, but does not cross-react with acepromazine, epinephr...
Antithrombin III activity (residual thrombin activity) in plasma from non-medicated or heparinized horses. Two synthetic substrate assays (fluorometric and chromogenic) were used to measure antithrombin-III (AT-III) activity (residual thrombin activity) in non-medicated and heparin (sodium) treated horses. In 18 non-medicated horses the fluorometric substrate assay (FSA) values were similar to previous reports but they reflected inconsistent trends and larger deviations in the heparin-treated groups (Group 2: 40 and 100 U/kg IV, n = 6; Group 3: 240 U/kg IV, n = 5; Group 4: 80 U/kg IV followed by 160 U/kg SC, n = 8) when compared to the chromogenic substrate assay (CSA) values. The CSA values for th...
Narcotic analgesics, their detection and pain measurement in the horse: a review. Narcotic analgesics produce pharmacological effects by interacting with specific opiate receptors. At least five major types of opiate receptors have been recognised. These include mu (morphine) and kappa (ethylketazocine) receptor types. Narcotic analgesics which interact with mu receptors produce locomotor and autonomic stimulation at doses that produce little or no analgesia. Therefore, use of these drugs as analgesics in equine medicine has not been very satisfactory. Theoretical considerations suggested that the role of kappa agonists in equine analgesia be investigated. Using a pure kapp...
Effects of distention and neostigmine on jejunal vascular resistance, oxygen uptake, and intraluminal pressure changes in ponies. The influence of distention (high baseline intraluminal pressure) and neostigmine methylsulfate on intestinal vascular resistance, oxygen uptake, and intraluminal pressure changes (rhythmic contractions) was studied in terminal jejunal segments, which were perfused at a constant rate, in 16 anesthetized ponies. When baseline intraluminal pressure was increased to 10 mm of Hg, the intestinal vascular resistance and amplitude of rhythmic contractions were increased. Neostigmine induced cyclic increases in amplitude of rhythmic contractions whether intraluminal pressure was 0 or 10 mm of Hg. Neos...
Pharmacological characterization of mare uterus motility with special reference to calcium antagonists and beta-2-adrenergic stimulants. 1. Uterine motility was studied in vitro in the myometrial tissue obtained from pregnant and non-pregnant mares. 2. The spontaneous contractions of the preparations were not modified by tetrodotoxin, by anticholinergics, antiadrenergics, histamine H1 and H2 blockers, antiserotoninergic and opioid antagonists; but disappeared in Ca2+ and Na+ free medium. 3. beta 2-adrenergic stimulants like salbutamol and hexoprenaline and the calcium channel blockers nifedipine and verapamil were effective inhibitors of the amplitude of phasic contractions (ID50S for salbutamol and nifedipine were 7.7 nM and 1...